With this proposal we request funds to continue our studies of epileptic mechanisms in the mammalian central nervous system. It has been known for many years that focal epileptic behavior is characterized by a synchronized discharge of cortical neurons and that this activity can spread throughout normal cortex. Our objective is to perform experiments that will clarify the mechanisms whereby normal neuronal circuits become involved in the epileptic process. This work will examine both the excitable properties of individual neurons and synaptic mechanisms. We will study in anesthetized cats the normal behavior of layer V nerurons and the response of these neurons to repetitive cortical stimulation to evoke seizure discharges using intracellular recording and the single electrode voltage clamp (SEVC). We are interested in the change in subthreshold ionic currents during the evolution of epileptic behavior in normal neurons. Experiments are proposed that will allow us to distinguish synaptic mechanisms from alterations in neuron excitability. Moreover, these experiments will allow us to validate our experiments in the in vitro cortical slice preparation. A second aim of this proposal is to use the neocortical slice to study in more detail the effects of graded changes in intracellular potassium concentration and the effects of synchronized electrical stimulation on the subthreshold currents of larger layer V neurons. We will also be able to test in more detail hypotheses about underlying mechanisms derived from the in vivo experiments. These experiments should add a significant piece of information to our understanding of the pathophysiologic mechanisms for focal epilepsy.